Role of GABRD Gene Methylation in the Nucleus Accumbens in Heroin-Seeking Behavior in Rats

Hong, Qingxiao; Xu, Wenjin; Lin, Zhang; Liu, Jing; Chen, Weisheng; Zhu, Huaqiang; Lai, Ming-Kuen; Zhuang, Dingding; Xu, Zeyuan; Fu, Dan; Zhou, Wenhua; Liu, Huifen

doi:10.3389/fphar.2020.612200

Cited by 12 publications

(6 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the study’s limitations are also acknowledged here: (1) In this study, we found that miR-23 was expressed in MM, while other miRNAs potentially targeting on uPA were expressed at very low or no levels in MM. To this end, we mainly focused on miR-23, while failing to uncover and explore the possible mechanisms for the deficency of expression of other miRNAs in MM; (2) Our results also showed that the methylation of the miR-23 promoter region may be a possible mechanism for the downregulation of miR-23 expression and the upregulation of uPA expression, but we failed to elucidate the possible mechanism of the methylation of the miR-23 promoter region, such as the relationship between DNA methylation transferase ( 41 , 64 – 66 ) with miR-23; (3) The promoter methylation of tumor suppressor genes represented by some miRNAs is an important mechanism for the occurrence and progression of malignant tumors ( 53 , 67 – 69 ). Small-molecular inhibitors such as DNA methyltransferase can not only upregulate the expression of some tumor suppressor genes, but also interact with the tumor suppressor genes ( 53 , 67 – 69 ).…”

Section: Discussionmentioning

confidence: 84%

Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA

Ran¹,

Xu²,

Wang³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

Multiple myeloma has a long course, with no obvious symptoms in the early stages. However, advanced stages are characterized by injury to the bone system and represent a severe threat to human health. The results of the present work indicate that the hypermethylation of miR-23 promoter mediates the aberrant expression of uPA/PLAU (urokinase plasminogen activator, uPA) in multiple myeloma cells. miR-23, a microRNA that potentially targets uPA’s 3’UTR, was predicted by the online tool miRDB. The endogenous expressions of uPA and miR-23 are related to disease severity in human patients, and the expression of miR-23 is negatively related to uPA expression. The hypermethylation of the promoter region of miR-23 is a promising mechanism to explain the low level of miR-23 or aberrant uPA expression associated with disease severity. Overexpression of miR-23 inhibited the expression of uPA by targeting the 3’UTR of uPA, not only in MM cell lines, but also in patient-derived cell lines. Overexpression of miR-23 also inhibited in vitro and in vivo invasion of MM cells in a nude mouse model. The results therefore extend our knowledge about uPA in MM and may assist in the development of more effective therapeutic strategies for MM treatment.

show abstract

Section: Discussionmentioning

confidence: 84%

Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA

Ran¹,

Xu²,

Wang³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Its high expression may suggest the adequate filtration of immune cells and immunity in the tumor microenvironment ( 37 ). GABRD is a gene that codes for a protein called gamma-aminobutyric acid (GABA) receptor delta subunit ( 38 ). Study has investigated the relationship between GABRD and cancer.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and immunological significance of an M1 macrophage-related gene signature in osteosarcoma

Mao¹,

Song

Ji³

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

As the most abundant infiltrating immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are pivotal in tumor development and treatment. The present investigation endeavors to explore the potential of M1 macrophage-related genes (MRGs) as biomarkers for assessing risk in individuals with osteosarcoma. RNA-sequence data and clinical data were derived from TCGA and GEO databases. The CIBERSORT method was utilized to discern subtypes of tumor-infiltrating immune cells. Identification of MRGs was achieved through Pearson correlation analysis. A prognostic risk model for MRGs was developed using Cox and LASSO regression analyses. A tripartite gene signature comprising CD37, GABRD, and ARHGAP25 was an independent prognostic indicator and was employed to develop a risk score model. The internal and external validation cohort confirmed the results. The area under the ROC curve (AUC) was determined for survival periods of 1 year, three years, and five years, yielding values of 0.746, 0.839, and 0.850, respectively. The C-index of the risk score was found to be superior to clinicopathological factors. GO/KEGG enrichment showed that the differences between high- and low-risk groups were predominantly associated with immune response pathways. Immune-related analysis related to proportions of immune cells, immune function, and expression levels of immune checkpoint genes all showed differences between the high- and low-risk groups. The qRT-PCR and Western blotting results indicate that CD37 expression was markedly higher in MG63 and U2OS cell lines when compared to normal osteoblast hFOB1.19. In U2OS cell line, GABRD expression levels were significantly upregulated. ARHGAP25 expression levels were elevated in both 143B and U2OS cell lines. In summary, utilizing a macrophage genes signature demonstrates efficacy in predicting both the prognosis and therapy response of OS. Additionally, immune analysis confirms a correlation between the risk score and the tumor microenvironment. Our findings, therefore, provide a cogent account for the disparate prognoses observed among patients and furnish a justification for further inquiry into biomarkers and anti-tumor treatment strategies.

show abstract

“…Rats underwent right jugular vein cannulation as previously described ( Hong et al, 2020 ). In brief, a silicone catheter (3.5 cm long, 0.5 mm inner diameter, 0.94 mm outer diameter) was inserted into the right external jugular vein.…”

Section: Methodsmentioning

confidence: 99%

Differential expression profiling of tRNA-Derived small RNAs and their potential roles in methamphetamine self-administered rats

Zhou

Hong

et al. 2023

Front. Genet.

Self Cite

View full text Add to dashboard Cite

Transfer RNA-derived small RNAs (tsRNAs) are a novel class of short, non-coding RNAs that are closely associated with the pathogenesis of various diseases. Accumulating evidence has demonstrated their critical functional roles as regulatory factors in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress. However, the underlying mechanisms by which tRFs & tiRNAs affect methamphetamine-induced pathophysiological processes are largely unknown. In this study, we used a combination of small RNA sequencing, quantitative reverse transcription-polymerase chain reaction (qRT‒PCR), bioinformatics, and luciferase reporter assays to screen the expression profiles and identify the functional roles of tRFs and tiRNAs in the nucleus accumbens (NAc) of methamphetamine self-administration rat models. A total of 461 tRFs & tiRNAs were identified in the NAc of rats after 14 days of methamphetamine self-administration training. Of those, 132 tRFs & tiRNAs were significantly differentially expressed: 59 were significantly upregulated, whereas 73 were significantly downregulated in the rats with methamphetamine self-administration. Decreased expression levels of tiRNA-1-34-Lys-CTT-1 and tRF-1-32-Gly-GCC-2-M2, as well as increased expression levels of tRF-1-16-Ala-TGC-4 in the METH group compared with the saline control were validated by using RT‒PCR. Then, bioinformatic analysis was performed to analyse the possible biological functions of tRFs & tiRNAs in methamphetamine-induced pathogenesis. Furthermore, tRF-1-32-Gly-GCC-2-M2 was identified to target BDNF using the luciferase reporter assay. An altered tsRNA expression pattern was proven, and tRF-1-32-Gly-GCC-2-M2 was shown to be involved in methamphetamine-induced pathophysiologic processes by targeting BDNF. The current study provides new insights for future investigations to explore the mechanisms and therapeutic methods for methamphetamine addiction.

show abstract

Role of GABRD Gene Methylation in the Nucleus Accumbens in Heroin-Seeking Behavior in Rats

Cited by 12 publications

References 62 publications

Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA

Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA

Prognostic and immunological significance of an M1 macrophage-related gene signature in osteosarcoma

Differential expression profiling of tRNA-Derived small RNAs and their potential roles in methamphetamine self-administered rats

Contact Info

Product

Resources

About